title: Induction of autophagy by cystatin C: a potential mechanism for prevention of cerebral vasospasm after experimental subarachnoid hemorrhage.
abstract: BACKGROUND
  Studies have demonstrated that autophagy pathways are activated in the brain after experimental subarachnoid hemorrhage (SAH) and this may play a protective role in early brain injury. However, the contribution of autophagy in the pathogenesis of cerebral vasospasm (CVS) following SAH, and whether up-regulated autophagy may contribute to aggravate or release CVS, remain unknown. Cystatin C (CysC) is a cysteine protease inhibitor that induces autophagy under conditions of neuronal challenge. This study investigated the expression of autophagy proteins in the walls of basilar arteries (BA), and the effects of CysC on CVS and autophagy pathways following experimental SAH in rats.
  
  
  METHODS
  All SAH animals were subjected to injection of 0.3 mL fresh arterial, non-heparinized blood into the cisterna magna. Fifty rats were assigned randomly to five groups: control group (n = 10), SAH group (n = 10), SAH + vehicle group (n = 10), SAH + low dose of CysC group (n = 10), and SAH + high dose of CysC group (n = 10). We measured proteins by western blot analysis, CVS by H&E staining method, morphological changes by electron microscopy, and recorded neuro-behavior scores.
  
  
  RESULTS
  Microtubule-associated protein light chain-3, an autophagosome biomarker, and beclin-1, a Bcl-2-interacting protein required for autophagy, were significantly increased in the BA wall 48 h after SAH. In the CysC-handled group, the degree of CVS, measured as the inner BA perimeter and BA wall thickness, was significantly ameliorated in comparison with vehicle-treated SAH rats. This effect paralleled the intensity of autophagy in the BA wall induced by CysC.
  
  
  CONCLUSIONS
  These results suggest that the autophagy pathway is activated in the BA wall after SAH and CysC-induced autophagy may play a beneficial role in preventing SAH-induced CVS.
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongfa
authors.initials: H
authors.lastname: Cai
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Jianke
authors.initials: J
authors.lastname: Li
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Wang
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Yu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D000071186:Beclin-1; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology; D055316:Cystatin C / Q000008:administration & dosage*; D057056:Cysteine Proteases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D055316:Cystatin C; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D057056:Cysteine Proteases